Acute Otitis Media (AOM) is the most common infectious disease among children to cause parents to seek medical care for their child. Children receive antibiotics to treat AOM which increases the emergence of antibiotic resistant bacteria. Temporary hearing loss is the most common complication; rarely there are intracranial complications. WHO estimates that 51,000 deaths/year are attributable to AOM in children younger than 5 years old and that chronic AOM (occurring in 65-330 million people) is the major cause of hearing loss in developing countries. Nontypeable Haemophilus influenzae (NTHi) bacteria accounts for 40-60% of AOM and recurrent AOM. A similar percentage of cases of acute sinusitis and rhinosinusitis, acute exacerbations of chronic bronchitis and acute pneumonia (in the developing world) are caused by NTHi.
Otitis prone (OP) children are defined as children with recurrent AOM, with at least 3 episodes in 6 months or 4 episodes in a 12-month time span. Each episode of AOM is typically followed by 4-12 weeks of otitis media with effusion (OME) during which time the child has diminished hearing and this often leads to temporary delayed speech and language development and can be associated with permanent hearing loss. Non otitis prone (NOP) children experience no ear infections or few ear infections, not meeting the OP definition. In the US alone, the economic burden of otitis media exceeded $5 billion/year in 1997 in medical treatment, surgical management, and loss of income for working parents. Thus, the impact on health costs and on lifestyle for the child and parents is very meaningful. OP children eventually lose their propensity to experience AOM, usually by age 5 years.
Due to the large costs related to AOM, there is a need for an effective preventive or prophylactic treatment. OP children do not always generate an efficient immune response and thus a vaccine that generates an immune response that efficiently destroys the pathogen is needed.
The disclosed invention provides a vaccine that produces humoral and cell mediated responses to NTHi for preventing ear infections, sinus infections, acute exacerbations of bronchitis and pneumonia. The invention provides epitopes that are of importance for generating an effective immune response to NTHi.
The invention further provides methods of vaccinating individuals with an effective NHTi vaccine.